Chemotherapy for Retinoblastoma

Chemotherapy (chemo) is the use of drugs to treat cancer. Chemo can be given systemically through the vein or locally to the eye to help treat retinoblastoma. 

Systemic chemotherapy

Chemo drugs can be injected into a vein (IV) or given by mouth. These drugs enter the bloodstream and reach throughout the body. This is known as systemic chemotherapy.

Systemic chemo is given in cycles, with each treatment followed by a rest period to give the body time to recover. Each chemo cycle typically lasts for a few weeks, and the total length of treatment is often several months.

Some of the chemo drugs used to treat retinoblastoma include:

• Carboplatin (Paraplatin)
• Cisplatin (Platinol)
• Vincristine (Oncovin)
• Etoposide (VP-16)
• Cyclophosphamide (Cytoxan)
• Topotecan (Hycamtin)
• Doxorubicin (Adriamycin)

Most often, 2 or 3 drugs are given at the same time. A standard combination is carboplatin, vincristine, and etoposide. Although, for very small tumors, using only carboplatin and vincristine may be enough. Other drugs might be used if these are not effective. Other combinations are being tested in clinical trials.

Local chemotherapy

Local administration of chemo can be given directly into the eye (intravitreal) or into the artery supplying the eye (intraarterial). Giving chemo this way, compared to systemic chemo, may reduce side effects.

Intraarterial chemotherapy

In this technique, a very thin catheter (a long hollow and flexible tube) is inserted into a large artery on the inner thigh and slowly threaded through the blood vessels all the way up into the ophthalmic artery, the vessel that carries blood to the eye. This is done with the child asleep under general anesthesia. The chemo is then given into the artery. Drugs that may be given intraarterially include:

• Carboplatin (Paraplatin)
• Melphalan (Alkeran)
• Topotecan (Hycamtin)

This process may then be repeated every few weeks, depending on how much the tumor shrinks.

Because chemo is put directly into the artery feeding the eye, doctors can use much smaller doses of chemo drugs (less than 10% of the doses used for systemic chemo). Therefore, there are fewer side effects from the chemo.

Results so far with this technique in eyes with advanced tumors have been good. In many cases it has allowed doctors to save an eye that otherwise would have needed to be removed.

Intravitreal chemotherapy

In this approach, a tiny needle is used to inject a chemo drug (typically melphalan or topotecan) directly into the vitreous humor, the jelly-like substance inside the eye. Chemo drugs given by this way include:

• Melphalan (Alkeran)
• Topotecan (Hycamtin)

This is sometimes used with other treatments to treat tumors that are widespread within the eye that have not responded to other treatments.

Ways chemotherapy is used

Chemotherapy (chemo) may be used to treat retinoblastoma in different situations:

• Chemoreduction: Chemo can be used first to shrink tumors that haven’t spread outside the eye. This makes it easier to treat the tumor with other methods like laser therapy, cryotherapy, or brachytherapy.
• Systemic chemotherapy: If the eye has already been treated or removed, but the tumor reached areas that make it more likely to spread or it has spread already, chemo may be used to help kill remaining cancer cells.
• Intrathecal chemotherapy: If the cancer has spread to the brain, chemo may also be given directly into the fluid around the brain and spinal cord. This is called intrathecal chemotherapy.
• High-dose chemo with stem cell transplant: If cancer spreads to other parts of the body, tumors might shrink at first with regular chemo but they often grow back. In these cases, doctors may give stronger chemo along with a stem cell transplant to try to cure the cancer.

Possible side effects of chemo

General side effects of chemo

Chemo drugs affect cells that grow fast. While cancer cells grow fast, other healthy cells in the body do too, for example blood-forming cells, hair cells, and cells that make up the lining of our gut. Damage caused by these drugs on fast-growing healthy cells results in side effects. The side effects of chemo depend on the types and doses of drugs used, and how long they are given.

Systemic chemo

Systemic chemo is more likely to affect other healthy cells through the body than chemo that is given locally. Possible short-term side effects include:

• Hair loss
• Mouth sores
• Loss of appetite
• Nausea and vomiting
• Diarrhea or constipation

Chemo can damage the bone marrow, where new blood cells are made. This can lead to low blood cell counts, which can result in:

• Increased chance of infections (from having too few white blood cells)
• Easy bruising or bleeding (from having too few blood platelets)
• Fatigue (from having too few red blood cells)

Most of these side effects tend to go away after treatment is finished. There are often ways to lessen these side effects. For example, drugs can be given to help prevent or reduce nausea and vomiting. Be sure to ask your child’s doctor or nurse about medicines to help reduce side effects and let them know if your child has side effects so they can be managed.

Chemotherapy can also have some longer-term side effects. For example, some drugs (such as etoposide) can increase the risk of later developing another type of cancer (such as leukemia). While this is a serious risk, it is not common, and the small increase in risk must be weighed against the importance of chemotherapy in treating retinoblastoma. For more on the possible long-term effects of treatment, see After Treatment for Retinoblastoma.

Local chemo

Intraarterial chemo: Much lower doses of chemo are used in this approach, so the side effects tend to be limited to the eye area. Possible side effects include:

• Swelling around the eye
• Detachment of the retina from the back of the eye
• Bleeding inside the eye
• Weakening of the muscles that move the eye
• Droopy eyelid
• Loss of eyelashes

While doctors hope that giving chemo directly to the eye area at lower doses will lead to better long-term health in survivors, it will take many years to know what side effects occur from these treatments. Treatment might affect the small blood vessels in and around the eye, which could affect vision as the child gets older. This approach also exposes the child to some radiation, because x-rays are used to help guide the catheter into place. It is not yet clear whether this affects a child’s risk of developing cataracts or cancer later in life.

Intravitreal chemo: As with intraarterial chemo, the side effects from this newer technique seem to be limited to the eye and nearby areas. Each treatment might damage the retina slightly, which might affect vision as the child gets older.

In the past, there was concern that placing a needle into the eye to give the chemo might open a small hole that could allow tumor cells to spread outside of the eye. However, studies have found that this risk is very low, and doctors now use techniques that lower this risk even further.

Possible side effects from specific chemo drugs

Along with the effects listed above, certain chemo drugs can cause specific side effects. For example: